Objective To verify whether Rev-erbα agonists can inhibit the inflammation of prostate tissue in mice induced by a high-fat diet, and to explore the mechanism of action. Methods C57B/ 6J male mice were divided into four groups: normal diet group, high-fat diet group, high-fat diet + SR9009 group, high-fat diet + control group. The body weight, peripheral blood cholesterol, triglyceride level, and prostate weight were measured. The prostate tissue was stained with hematoxylin-eosin (HE), subjected to transcriptome sequencing, and the expression levels of IL-6, IL-8, IL-1β, NF-κB-P65, and CCL21 were evaluated by immunohistochemistry. Results Compared with the normal diet group, the body weight, prostatic index, and the serum TG and TC levels of mice in the high-fat diet group were significantly increased, and the body weight, prostatic index, and serum TG and TC levels of the mice in the high-fat diet + SR9009 group were significantly lower than those of the high-fat diet + control group mice. HE staining showed that inflammatory cell infiltration into the prostate tissue of the mice in the high-fat diet group was increased compared with the normal diet group, and inflammatory cell infiltration into the prostate tissue of the mice on the high-fat diet was reduced after intervention with SR9009. The expression levels of Ccl21a, Ccr7, Tlr4, Il6, Il1b, and Cxcr2 were higher in the high-fat diet group than in the normal diet group, as demonstrated by heatmap analysis, but these expression levels were lower in the high-fat diet + SR9009 group than in the high-fat diet + control group. The differences in the expression intensity of IL-6, IL-8, IL-1β,NF-κB-P65, and CCL21a in the prostate of the four groups of mice were consistent with the differences in the sequencing result. Conclusions The circadian clock protein Rev-erbα can regulate the inflammation level of prostate tissue induced by a high-fat diet through the NF-κB pathway.