Objective: Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to non-alcoholic steatohepatitis, which is characterized by hepatic inflammation that can progress to fibrosis, cirrhosis and hepatocellular carcinoma. The progression of NAFLD is still poorly understood. Visfatin, an adipocytokine, was reported to induce pro-inflammatory cytokines and can be associated with liver fibrosis. We investigated the role of visfatin on hepatic inflammation and fibrosis in a methionine-choline-deficient (MCD) diet induced steatohepatitis mouse model. Methods: Three groups of 8-week-old male C57BL/6J mice were studied for 2 weeks: 1) saline-injected control diet group; 2) saline-injected MCD diet group; and 3) visfatin-injected MCD diet group (n=8/group). Mice were intravenously injected every day with saline or 10 μg of recombinant murine visfatin for 2 weeks. Histologic assessment of liver, and biochemical and molecular measurements of endoplasmic reticulum (ER) stress, oxidative stress, inflammation, and fibrosis were performed in livers from these animals. Results: Treatment with visfatin increased liver weight of MCD-diet fed mice without changing ALT, AST and liver fat content. Visfatin elevated the serum CC chemokine ligand (CCL) 20 and CXC chemokine ligand (CXCL) 8, and increased hepatic mRNA expression of CXC chemokine receptor (CXCR) 1, CXCR2, CXCL2, and CCL2. The intravenous injection of visfatin increased inflammatory cell infiltration (indicated by F4/80, CD68, ly6G, and CD3 mRNA expression) in the liver. Visfatin also increased the expression of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) and activated the fibrosis markers (cTGFβ, TIMP1, collagen 1A2, collagen 3A2, αSMA, Fibronectin, and Vimentin). Livers of mice injected with visfatin showed an upregulation of the ER stress and oxidative stress and activation of JNK signaling. Conclusion: These results suggest that visfatin aggravates hepatic inflammation with inducing ER stress and oxidative stress, and exacerbates fibrosis in MCD diet fed mouse model of steatohepatitis.