〔Abstract〕 Objective To study the possible regulation mechanism of overexpression of salt-inducible kinase 1(SIK1) on hepatic lipid metabolism disorders(LMD) in obese rats induced by high-fat diet(HFD). Methods Forty SD rats were randomly divided into Control group(10 cases) and modeling group(30 cases). They were fed with HFD for 12 weeks, and those with successful modeling were randomly divided into Obesity group, Obesity+LV group and Obesity+LV-SIK1 group. Obesity+LV group and Obesity+LV-SIK1 group were injected with lentiviral blank plasmid and lentivirus-mediated SIK1 overexpression plasmid through tail vein, respectively, and then fed with HFD for 8 weeks. Fasting blood from tail vein was applied to detect levels of liver function indexes [(alanine aminotransferase, ALT),(aspartate aminotransferase, AST)], lipid metabolism indexes [(total cholesterol, TC),(triglycerides, TG),(high density lipoprotein cholesterol, HDL-C),(low density lipoprotein cholesterol, LDL-C)]and inflammatory cytokines [(tumor necrosis factor-α,TNF-α),(inducible nitric oxide synthase, iNOS),(interleukin-6,IL-6), IL-10]. The pathological damage and fat accumulation in liver tissues were observed by HE staining and oil red O staining. The expression of apoptosis marker proteins(Caspase-3, Caspase-9) and adipogenesis genes(SREBP-1 c, FASN, ACC1) in liver tissue was detected by Western blot. Results Compared with Control group, body mass, levels of serum ALT, AST, TC, TG, LDL-C, TNF-α, iNOS, IL-6 and IL-10 increased in Obesity group(P<0.05), while HDL-C level decreased(P<0.05). There was significant structural damage and fat accumulation in liver tissues, and the expression levels of cleaved-Caspase-3/Caspase-3, cleaved-Caspase-9/Caspase-9, SREBP-1 c, FASN and ACC1 proteins in liver tissues increased(P<0.05). Compared with Obesity group, body mass, levels of serum ALT, AST, TC, TG, LDL-C, TNF-α, iNOS and IL-6 decreased in Obesity+LV-SIK1 group(P<0.05), while levels of HDL-C and IL-10 increased(P<0.05). The structure destruction and fat accumulation in liver tissues reduced. The expression levels of cleaved-Caspase-3/Caspase-3, cleaved-Caspase-9/Caspase-9, SREBP-1 c, FASN and ACC1 proteins decreased(P<0.05). Conclusion There are damage and large amount of fat accumulation in liver tissues of HFD induced obese rats. SIK1 overexpression can reduce the expression of adipogenesis genes, improve LMD, and reduce damage to liver tissue caused by fat accumulation.