The clinical therapy for cyclosporine A (CsA)-induced gingival hyperplasia (GH) and the pathological changes in hyperplastic gingival tissues were investigated. Nine cases of CsA-induced GH after renal transplantation were subjected to periodontal non-surgical treatment and surgical treatment and were followed up. Gingival index (GI), dental plaque index (PLI) and GH degree (GHD) at different time points were measured. Under light and electron microscopy, the pathological changes in hyperplastic gingival tissues were observed. The CsA concentrations in gingival tissues and blood were determined by using fluorescence polarization immunoassay with TDFL monoclonal antibody. The results showed that GI, PLI and GHD in patients with GH declined after periodontal treatment. Two patients suffered from different degrees of GH during the 6 months to 54 months post-transplantation. Under transmission electron microscopy, fibroblasts in the hyperplastic gingival tissues were enlarged, cytoplasmic rough endoplasmic reticula were abundant and expanded slightly, and a few fibroblasts with early apoptotic changes were seen. The concentrations of CsA in hyperplastic gingival tissues were from 351.00 to 1345.47 ng/mL, which were significantly higher than in the blood of the same patients taken at the same time points. It was concluded that GI and PLI declined after periodontal treatment in combination with surgical treatment in patients taking CsA for a long time, but in some patients, GH recurred. The fact that the concentration of CsA in hyperplastic gingival tissues is higher than in blood awaits further studies.