Objective To explore the dynamic changes of oxidative stress and cytokines in Mongolian gerbils with nonalcoholic fatty liver disease (NAFLD) and their significance. Methods Forty-eight healthy male gerbils were randomly divided into normal group and model group, 24 in each group. Gerbils of the model group were fed with high fat diet while those of the normal group with normal diet. Eight gerbils in each group were killed at the end of 4 w, 8 w and 16 w, respectively. MDA content and SOD, GSH-PX and T-AOC activity in the liver tissue were detected by chemical method, and serum TNF-α, INF-γ and IL-10 levels were determined using liquid suspension chip. Results With the development of NAFLD, MDA content in liver increased gradually, and the MDA contents were all significantly higher than those of the normal group (P<0.01); T-AOC level slightly increased, and then decreased, the levels at 4 w and 16 w were markedly decreased compared with those of the normal group (P<0.05); SOD level was significantly increased and then markedly reduced, the level of the model group at 4 w was significantly increased (P<0.05), while that at 8 w and 16 w were significantly decreased (P<0.05, P<0.01). The level of GSH-PX was decreased gradually, the levels at 8 w and 16 w were significantly lower than those of the normal group (P<0.05). With the progression of NAFLD,serum TNF-α and IFN-γ were increased gradually, while the level of IL-10 decreased gradually, and the levels at 8 w and 16 w were significantly lower than those of the normal group (P<0.05, P<0.01). Conclusions The oxidative stress-related indicators and inflammatory cytokines in the gerbil NAFLD models induced by high fat diet are significantly changed as simple fatty liver develops into steatohepatitis, liver fibrosis and cirrhosis, and participate in the development and progression of NAFLD.