Objective To explore the effects of polarization of CD4⁺T cells during the course of inflammatory reaction of renal interstitial fibrosis. Methods Twenty-four SD rats that underwent unilateral ureteral obstruction (UUO) were randomly divided into the sham-operation group, UUO 3 d group, and UUO 7 d group. The degree of fibrosis of renal tissue was observed by H-E and MASSON staining. CD4⁺T cells in peripheral blood were separated by immunomagnetic beads and cultured for 3 d under the stimulation of CD3/28-IL-2. The in vitro proliferation and polarization of CD4⁺T cells of rats with UUO and normal rats were compared by flow cytometry. The difference of transcription factor was detected by PCR. Results The fibrosis of renal tissue and infiltration of lymphocytes aggravated and the proliferation of CD4⁺T cells increased after UUO (P<0.05). Compared with normal rats, IL17A⁺CD4⁺T/CD4+T and CD4⁺CD25⁺Foxp3⁺/CD4⁺T ratios of rats with UUO were higher (P<0.05). Detection of upstream transcription factors of CD4⁺ T subsets showed that pro-inflammatory genes RORγt and T-bet significantly increased with time after UUO; anti-inflammation gene Gata-3 decreased; and inflammation regulation gene Foxp3 increased (P<0.05). Conclusion Renal interstitial fibrosis can promote CD4⁺T cell to proliferate and release various pro-inflammatory factors and aggravate inflammatory reaction and disease.