Objective To investigate the mechanism of trace element strontium on alleviating non-alcoholic fatty liver disease (NAFLD) in rats.Methods Fifty SD rats were randomly divided into five groups. The control group was fed with ordinary diet and the other four groups were fed with a high fat diet. From the 6th week, rats in the strontium 18 mg/L and 36 mg/L groups were fed with water with strontium in concentration of 18 mg/L and 36 mg/L respectively. These two groups were separately given strontium water (3 mL/kg b.w.) by gavage from the 11th week, while the Simvastatin group was given simvastatin (10 mg/kg b.w.) by gavage from the 11th week. Rats in other groups were given matching normal saline by gavage at the same period. The rats were killed and the TG, TC, LDL-C levels in their serum and the TG, TC levels in the liver were detected at the end of the 14th week. The lipid accumulation in the liver tissue was observed using oil red O staining. The protein expression levels of GRP78, SREBP2, HMGCR and LDLr in the liver tissue were assessed with immunohistochemical staining.Results The levels of serum TC, LDL-C and liver TC, TG in the NAFLD group were significantly higher than that of the control group (P<0.05). The levels of serum TC, LDL-C and liver TC, TG in the strontium 36 mg/L group were significantly lower than that of the NAFLD group (P<0.05). ORO staining showed that lipid accumulation in liver increased abnormally in the NAFLD group compared with the control group, while the lipids accumulation in the liver decreased obviously in the strontium 18 mg/L group, 36 mg/L group and simvastatin group compared with the NAFLD group to a different degree. Immunohistochemical staining showed that the protein expression levels of GRP78, SREBP2, HMGCR and LDLr in the NAFLD group, those of GRP78, SREBP2 and LDLr in the strontium 18 mg/L group, those of LDLr in the strontium 36 mg/L group and those of SREBP2 and LDLr in the Simvastation group significantly increased compared with those of the control group (P<0.05). The protein expression levels of GRP78, SREBP2 and HMGCR in the strontium 36 mg/L group decreased obviously compared with those of the NAFLD group, while those of LDLr in the strontium 36 mg/L group increased compared with those of the NAFLD group (P<0.05). The protein expression levels of GRP78 and HMGCR in the simvastatin group decreased compared with the NAFLD group(P<0.05). The protein expression levels of GRP78, SREBP2, HMGCR and LDLr in the strontium 18 mg/L group had no significant difference compared with the NAFLD group (P>0.05).Conclusions Intake of trace element strontium at high concentration for long time can alleviate the disorder of lipid metabolism and non-alcoholic fatty acid liver disease (NAFLD) in rats. Its mechanism is probably related to its adjusting of endoplasmic reticulum stress, the activity of HMGCR and the function of LDLr.