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Background: Mesenchymal stem cell (MSC) transplantation is a promising therapy for kidney repair. This study compared the regenerative effects of feline MSCs (fMSCs) and telmisartan, a renin-angiotensin blocker (RAB), in a feline model of chronic kidney disease (CKD). Methods: The fMSCs were obtained from 35 Persian cats with CKD and characterized by CD44, CD90, and CD105 markers by using real-time RT-qPCR. The cats were randomly allocated to four groups, fMSCs injection (first group), telmisartan administration (second group), no treatment (third group), and healthy controls (fourth group). The study was conducted in Kerman province from December 2018 to December 2019. The factors that may affect the risk of CKD, such as age, weight, and history of kidney diseases, were considered as independent variables. The presence or absence of CKD was the dependent variable. The cats were followed up for 120 days and evaluated by physical examination, glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum creatinine (SCr), serum urea, alanine transaminase (ALT), urine specific gravity (SG), and kidney histopathology. Statistical analysis was performed using SPSS software (version 20) with two-way ANOVA and Tukey test. P<0.05 was considered statistically significant. Results: The fMSCs group showed significant improvement in GFR, BUN, SCr, serum urea, SG, and kidney histology compared to the other groups. The fMSCs group also showed increased expression of CD44, CD90, and CD105 genes in the kidney tissue, indicating enhanced stem cell activity. The telmisartan group showed modest improvement in blood pressure and proteinuria, but no significant effect on other parameters. fMSCs transplantation can restore the kidney function and structure in cats with CKD by modulating the apoptosis and proliferation of renal cells. The telmisartan patients benefited from the anti-hypertensive and anti-proteinuric effects of the drug, but not from its anti-fibrotic or anti-inflammatory effects. Conclusion: fMSCs transplantation was more effective than telmisartan in improving kidney function and reducing kidney damage in cats with CKD. fMSCs may be a potential therapeutic option for CKD patients. [ABSTRACT FROM AUTHOR]