Objective To investigate the relationship between the clinical factors of renal transplant recipients medicated with cyclosporine A (CsA) and gingival overgrowth (GO), so as to evaluate the association of serum cyclophilin A (CyPA) with CsA-induced GO. Methods Totally 65 renal transplant recipients were enrolled in this study. The degrees of GO were evaluated using gingival overgrowth index (GOI) and the patients were subsequently grouped into overgrowth (GO+) and non-overgrowth (GO-). The age, gender, medication duration, dosage of immunosuppressive agents, serum concentrations of CsA and CyPA, creatinine, ureal and gingival assessments were compared between the two groups. The possible correlation between CyPA level and the development and severity of CsA-induced GO was also identified. Results The number of GO+ subjects (GOI≥30) was 14 (21.54%) in the present patients. There were no significant differences in age, gender and medication duration, dosage of immunosuppressive agents, serum concentration of CsA, serum creatinine or ureal level between the two groups. Serum CyPA level in GO+ group was significantly lower than that in GO- group (0.23 \[0.16-0.30\] ng/mL vs 0.34\[0.22-0.54\] ng/mL, P=0.04). Serum CyPA concentration was negatively correlated with GO degree (r=-0.264, P=0.03), and was not correlated with dosage or concentration of CsA (r=-0.014, P=0.91; r=0.012, P=0.93). In addition, the patients with GO presented a significantly high plaque index and papilla bleeding index than those without GO (1.41±0.27 vs 1.15±0.34, P=0.01; 0.49±0.30 vs 0.25±0.11, P=0.01). Conclusion Development of CsA-induced GO may be due to a co-work of both local and system factors; serum CyPA level might be an risk factor for CsA-induced GO independent to dosage and serum level of CsA, which may help to detect GO in clinic.