Objective To detect the level of adiponectin (APN) and liver expression of silent information regulator 1 (SIRT1) in rats in early stage of diabetic mellitus (DM) and investigate the role of SIRT1 in the regulation of APN. Methods A total of 42 Sprague-Dawley rats were randomly divided into normal control group (n=10), DM model group (n=10), DM+resveratrol (RES) group (n=11) and DM+niacin amide (NIA) group (n=11). Rat DM model was established by an injection of streptozocin after 5 weeks′ high fat diet. Basic metabolic indices, serological parameters, and pathological changes of liver tissues by HE staining were used to identify the model establishment. The plasma level of APN was detected by ELISA reagent kit. Western blotting and RT-PCR were employed to measure the expression of SIRT1 and APN receptor AdipoR2 at protein and mRNA levels in the liver tissues. SPSS statistics 19.0 was used to perform the statistical analysis. Chi-square test and Student′s t test were employed for intergroup comparison based on different data types. Results Compared with the DM group, the DM+RES group had significantly lower fasting blood glucose (FBG; P<0.05), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C; P<0.05), and triglycerides (TG; P<0.05), but obviously elevated high-density lipoprotein cholesterol (HDL-C; P<0.01), and slightly increased APN (P>0.05). The DM+NIA group had remarkable higher TC and LDL-C (P<0.05), and obviously decreased APN (P<0.05) when compared with the DM group. Pathological observation displayed that obvious infiltration of inflammatory cells and even degeneration in the liver tissues of the DM group, attenuated cell degeneration in the DM+RES group, and dispersed lipid droplets in the liver cells of the DM+NIA group. Western blotting showed the protein levels of AdipoR2 and SIRT1 were increased (both P<0.05) and that of WISP-1 was decreased in the DM+RES group (P<0.05), while the levels were reduced in the DM+NIA group. Similar trends were seen in the mRNA expression levels of the 2 molecules(P<0.05). Conclusion In the development of early liver damage in DM rats, the signaling molecules of SIRT1 may modulate the expression of AdipoR to regulate APN level, and then participate in the pathophysiological evolution of endocrine system after DM.