The global rise of obesity and obesity-associated complications such as type 2 diabetes and cardiovascular disease has become a major public health concern. The etiology and pathogenesis of these obesity- related diseases are caused by multiple factors, and the free fatty acid receptors may play important roles. G protein coupled receptor 84 (GPR84) is a medium-chain (C9-C14) fatty acid-sensing receptor. However, its functions in obesity and metabolic diseases remain unclear. In this research, we established a high-fat diet induced obesity model in wild type and GPR84 knockout mice. Compared with WT mice, GPR84 knockout mice have similar levels of food intake, body weight, oral glucose tolerance test and insulin tolerance test both on normal chow diet and high-fat diet. GPR84 deficiency in mice did not affect fasting blood glucose level, insulin, triglyceride, low density lipoprotein cholesterol (LDL-c) and high density lipoprotein cholesterol (HDL-c). There were no genotypic differences in tissue mass, lipid synthesis, fatty acid oxidation and lipogenesis in mice on normal chow diet or high-fat diet. However, the concentration of total cholesterols (TC) was significantly reduced and scavenger receptor class B typeⅠ(SR-BⅠ) was significantly increased in GPR84 knockout mice compared with WT mice on high-fat diet. These results indicate that GPR84 may not be involved in glucose and lipid metabolism in mice; instead, it may play a role in hypercholesterolemia caused by high cholesterol.