OBJECTIVE: To evaluate the effectiveness of Sini powder for the treatment of non-alcoholic fatty liver disease(NAFLD) in rats and the molecular mechanisms involved.METHODS: A rat model of stress-induced NAFLD was established by a combination of long-term tethering and feeding of a high-fat, high-calorie diet. These rats were then intragastrically administered with either simvastatin, Sini powder, or vehicle for 1 week. The body mass and field test scores for each group were recorded weekly. Serum aspartate aminotransferase and alanine aminotransferase activities, and triglyceride, total cholesterol,and free fatty acid concentrations were measured.Liver tissue histopathology was examined on hematoxylin and eosin-stained paraffin sections and oil red O-stained frozen sections. The hepatic m RNA expression of nuclear factor kappa-B(NF-κB),NOD-, LRR-, and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC), and caspase-1 were measured by reverse transcription-polymerase chain reaction(RT-PCR). The hepatic protein concentrations of NF-κB and NLRP3, ASC, caspase-1, interleukin-1β(IL-1β), interleukin-6(IL-6), and the serum concentrations of IL-1β and IL-6 were measured by enzyme-linked immunosorbent assay.RESULTS: Compared with the Blank group, rats in the Compound model group showed significant pathologic manifestations of NAFLD, and the expression of NF-κB, NLRP3, ASC, caspase-1, IL-1βand IL-6 were significantly higher(all P < 0.01). Both simvastatin and Sini powder significantly ameliorated the NAFLD pathology and the abnormal expression of NF-κB, NLRP3, ASC, caspase-1, IL-1β, and IL-6(all P < 0.01).CONCLUSION: Sini powder inhibits the inflamma-tory response in rats with NAFLD, which is mediated by NF-κB/NLRP3, IL-1β, and IL-6, reduces the effects of psychological stress, and improves lipid metabolism. Therefore, Sini powder may be effective for the treatment of stress-related NAFLD through multiple mechanisms.