OBJECTIVE: This study is to research the role of follicular helper T (TFH) cells and follicular regulatory T (TFR) cells in the progression of lupus nephritis (LN). METHODS: A total of 33 active LN patients, 30 stable LN patients, and 30 healthy controls (HC) were included in this study. The frequencies of TFH, TFR, T cell Ig and ITIM domain (TIGIT) + TFR, and CD226 + TFR cells in peripheral blood were measured using flow cytometry. The distribution and proportion of TFH and TFR cells in renal tissue were assessed using a multiplex immunohistochemical. RESULTS: Active LN had a significantly lower TFR and TFR/TFH ratio in peripheral blood than HC and stable LN. TIGIT + TFR was lower in active LN, while CD226 + TFR was higher. In LN, TFR and TFR/TFH ratio showed a negative correlation with creatinine (CREA), but a positive correlation with endogenous creatinine clearance (Ccr). TFH and TFR mainly infiltrated the renal interstitium or surrounding renal tubules and participated in the formation of ectopic lymphoid-like structures in active LN. In active LN, TFH cells in renal tissue were higher than in control renal tissue. The tissue TFH showed a positive correlation with the activity index, CREA, but a negative correlation with Ccr. The tissue TFR/TFH ratio showed a negative correlation with the activity index, CREA, but a positive correlation with Ccr. CONCLUSION: In active LN, the proportions of TFR cells in peripheral blood are reduced and function is impaired. In active LN, TFH and TFR imbalances have been observed and are associated with renal injury.