Abstract:Objective To investigate the mechanism of Linggui Zhugan Decoction regulating macrophage polarization to improve non-alcoholic steatohepatitis (NASH). Methods A total of 24 SPF male SD rats, aged 6-8 weeks and weighing 180-200 g, were divided into blank group, model group, Linggui Zhugan Decoction group, and Polyene Phosphatidylcholine Capsules (Yishanfu) group according to random number table method, with six rats in each group. NASH rat model was induced by high fat diet. Linggui Zhugan Decoction group was given 3.465 g/(kg·d) Linggui Zhugan Decoction Formula Granules intragastric administration, Yishanfu group was given 143.640 mg/(kg·d) Yishanfu suspension intragastric administration, blank group and model group were given equal amounts of distilled water intragastric administration, once a day, for a total of four weeks. The changes of body weight, liver wet weight, liver index, liver histopathology, and the levels of M1 and M2 macrophages in the liver of rats were observed after treatment. Results Compared with blank group, the body weight, liver wet weight, and liver index of model group were increased, and the differences were highly statistically significant (P<0.01). Compared with model group, the body weight, liver wet weight, and liver index of Linggui Zhugan Decoction group were decreased, and the differences were highly statistically significant (P<0.01). Compared with blank group, the liver color of model group was whiter, hepatocyte balloon-like degeneration, steatosis, and inflammatory cell infiltration were increased. Compared with model group, the liver color of Linggui Zhugan Decoction group was obviously restored, hepatocyte balloon-like degeneration, steatosis, and inflammatory cell infiltration were decreased. Compared with blank group, M1-type macrophages in liver of model group were increased, the differences were highly statistically significant (P<0.01). Compared with model group, liver M1-type macrophages in Linggui Zhugan Decoction group were decreased, and the differences were highly statistically significant (P<0.01). There were no significant differences in liver M2-type macrophages between model group and blank group (P>0.05). There was no significant difference in liver M2-type macrophages between Linggui Zhugan Decoction group and model group (P>0.05). Conclusion Linggui Zhugan Decoction can significantly relieve the lipid deposition and inflammatory cell infiltration of NASH rat hepatocytes, which may play a role in the treatment of NASH by regulating macrophage polarization.