Objective To explore the expression and changes of serum irisin in adenine-induced chronic kidney disease (CKD) model, and the role of irisin and related pathway in CKD renal fibrosis. Methods Twenty male SD rats were randomly divided into a control group and a model group (CKD group) using a simple randomization method, with 10 rats in each group. At the end of the 2nd and 4th week, biochemical indicators, serum irisin and serum bone morphogenetic protein 7 (BMP7) levels, renal pathologic changes and interstitial fibrosis of renal tubules were measured in two groups of rats. The protein expression levels and messenger RNA (mRNA) expression levels of alpha-smooth muscle actin (α-SMA), collagen type I (Col-Ⅰ), BMP7, and Smad1 in rat kidney tissue were detected and compared. Results Compared with the control group at the end of the 2nd and 4th week, the CKD group showed that the serum creatinine (Scr), serum urea nitrogen (BUN), and 24-hour urinary protein level were increased (P<0.05), the protein expression levels and mRNA expression levels of α-SMA and Col-Ⅰ were increased (P<0.05), while the serum irisin and serum BMP7 were decreased (P<0.05), the protein expression levels and mRNA expression levels of BMP7 and Smad1 were reduced (P<0.05). Compared with the end of the 2nd week, the CKD group at the end of the 4th week showed that the serum Scr, serum BUN, and 24-hour urinary protein level were increased (P<0.05), the protein expression levels and mRNA expression levels of α-SMA and Col-Ⅰ were increased (P<0.05), while the serum irisin and serum BMP7 were decreased (P<0.05), the protein expression levels and mRNA expression levels of BMP7 and Smad1 were reduced (P<0.05). Compared to the control group, the renal tissue structure of the CKD group showed significant structural disorders and interstitial fibrosis of the renal tissue, which worsened over time. Serum irisin was negatively correlated with α- SMA and Col - Ⅰ (r=−0.917, −0.902, P<0.001) respectively, while serum irisin was positively correlated with serum BMP7 (r=0.842, P<0.001); Kidney tissue BMP7 was positively correlated with Smad1 (r=0.884, P<0.001). The cluster heat map showed that compared with the control group, BMP7 and recombinant fibronectin type Ⅲ domain containing were significantly decreased, α-SMA and Col-Ⅰ were significantly increased in CKD group; recombinant fibronectin type Ⅲ domain containing were positively correlated with BMP7, and negatively correlated with α-SMA and Col-Ⅰ. Conclusions irisin may be involved in the process of renal fibrosis in adenine-induced CKD via the BMP7/Smad1 axis. This will provide new ideas for the prevention and treatment of renal fibrosis.