OBJECTIVE To identify the biological reaction of soluble interleukin-6 receptor (sIL-6R) in the vitreous of patients with proliferative diabetic retinopathy (PDR). METHODS The subjects were 45 patients (45 eyes) with vitreoretinal diseases. The patients were divided into three groups: the PDR group comprised 28 patients (28 eyes) with PDR; the pre-proliferative diabetic retinopathy (PPDR) group comprised seven patients (seven eyes) with PPDR combined with diabetic macular edema; and the nondiabetic group comprised ten patients (ten eyes) with idiopathic macular hole or idiopathic epiretinal membrane. Vitreous samples were obtained at vitrectomy. sIL-6R, vascular endothelial growth factor (VEGF), and protein concentration in vitreous samples were determined by enzyme-linked immunosorbent assay (ELISA). sIL-6R levels in serum were also determined by ELISA in nine of the 28 patients with PDR and in six healthy volunteers as controls. RESULTS In vitreous fluid, the levels of sIL-6R in the PDR group, PPDR group, and nondiabetic group were 612.7 +/- 233.8 (mean +/- SD), 746.3 +/- 523.1, and 215.4 +/- 98.3 pg/ml, respectively. Vitreous levels of sIL-6R in the PDR and PPDR groups were significantly higher than those in the nondiabetic group (PDR group, P < 0.0001; PPDR group, P < 0.01). In serum, the levels of sIL-6R were 39.38 +/- 9.43 ng/ml in the PDR group and 22.84 +/- 5.32 ng/ml in the control group. sIL-6R levels in serum in the PDR group were significantly higher than those in the control group (P < 0.01). A partial correlation analysis showed a significant correlation between the levels of sL-6R and VEGF in the vitreous in the PDR group (r = 0.34, P < 0.05). CONCLUSIONS We conclude that the level of sIL-6R in vitreous fluid can be considered as a biomarker of PDR.