To investigate the differential expression of complement C4b and transthyretin in proliferative vitreoretinopathy (PVR).It was a controlled experimental study. Human vitreous samples of 5 patients with PVR were analyzed by using two-dimensional gel electrophoresis and mass spectrometry, and the results were compared with those from normal control vitreous obtained from donor eyes. An in vivo model of PVR was created by intravitreous injection of cultured rabbit retinal pigment epithelial (RPE) cells. The vitreous of PVR models were analyzed by enzyme linked immunosorbent assay (ELISA) to confirm the proteomic results from the PVR patients.Seventy nine various proteins were expressed differently between PVR and normal vitreous, among which nine up-regulated proteins including complement C4b, transthyretin (TTR), and 7 albumins were identified by mass spectrometry. The up-regulation of complement C4b and TTR in PVR patients was also confirmed by ELISA. The concentration of complement C4b and TTR in normal vitreous were (20.18 ± 1.97) mg/L and (88.58 ± 8.84) mg/L respectively, in PVR patients were (38.1 ± 5.79) mg/L and (112.57 ± 6.89) mg/L respectively, difference significantly between these two groups (C4b: t = 11.54, TTR:t = 9.24; P < 0.05).Differences of complement C4b and TTR expression were observed between PVR and normal vitreous. These results have lead to the assumption that there is a connection between elevated concentrations of both complement C4b and TTR and the pathogenesis of PVR and further studies on the functions of these proteins are required.