Objective To investigate the effect and molecular mechanism of Dendrobium candidum polysaccharides on chronic atrophic gastritis (CAG) induced by N?methyl?N′?nitro?N?nitrosoguanidine (MNNG) in rats. Methods To establish the CAG model, Wistar rats were first provided free access to MNNG drinking solution containing 167 g/ mL distilled water for 8 weeks. Then, the high?dose Dendrobium candidum polysaccharide group was given 1. 34 g/kg of raw drug per day by gavage, the medium?dose group was given 0. 67 g/ kg, and the low?dose group was given 0. 335g/ kg. Weiyangshu granules at 4. 0 g/ kg were administered to the groups every day. Normal saline was administered to a model group, in which no intervention was performed. Twelve weeks after the treatment, the stomach tissue was removed, and subjected to analyses of the histology and levels of stomach gastrin release, interleukin?6, PCNA, tumor necrosis factor alpha, Janus kinase 2, and activating factor?3/ tyrosine phosphorylation?3. Results 1) After 12 weeks of treatment, the body weight of the model group was significantly lower than that of the normal group ( P < 0. 01).. The weights of the three groups with different dosages of Dendrobium polysaccharide and the Yangweishu group were significantly higher than that of the model group ( P < 0. 05). The body weight of the high?dose Dendrobium candidum polysaccharide group was significantly higher than that of the Yangweishu group ( P < 0. 05). (2) The grade of inflammation in the model group was significantly higher than that in the normal group ( P < 0. 01). The numbers and thicknesses of chief cells and parietal cells in the model group were significantly lower than those in the normal group ( P < 0. 05), while the number of glands in the normal group and the thickness of the rats were thick and thick chief cells and parietal cells were significantly higher than those in the model group ( P < 0. 05). In the three dose groups of Dendrobium candidum polysaccharide, the grade of inflammation of gastric tissue, number of glands, gland thickness, chief cell, and parietal cells in the Yangweishu group recovered significantly ( P < 0. 05). (3) The level of GAS in the model group was significantly lower than that in the normal group. The amount of IL?6 in the model group was significantly higher than that in the model group ( P < 0. 05). The level of IL?6 in the normal group was significantly lower than that in the model group ( P < 0. 05). The levels of GAS in the three dosage groups of Dendrobium candidum polysaccharide and the Yangweishu group were significantly higher than that in the model group ( P < 0. 05). The IL?6 content in the high?dose group of Dendrobium candidum polysaccharide was significantly lower than that in the model group ( P < 0. 05). (4) The PCNA mRNA and TNF?α mRNA levels in normal model rats were significantly lower than those in the normal model group ( P < 0. 05). PCNA mRNA and TNF?α mRNA levels in the high?dose group of Dendrobium candidum polysaccharide were significantly lower than those in the model group ( P < 0. 05). (5) The expression of JAK2/ β?actin and p?STAT3/ STAT3 in the high?dose group of Dendrobium candidum polysaccharide was significantly lower than that in the model group ( P < 0. 05). Conclusions Dendrobium officinale polysaccharide has good protective and reversal effects on CAG rats, effectively restoring weight and alleviating gastric mucosal atrophy. One of its mechanisms may be to improve gastric mucosal pathology by inhibiting the activation of the JAK2/ P?STAT3 signaling pathway.