To detect the expression of collagen III, CTGF and TNF-alpha in human fetal membranes with premature rupture of fetal membranes (PROM) and non-PROM, and explore their roles in the pathogenesis of PROM.Fifty women with PROM were enrolled in this study, and divided into preterm premature rupture of membranes (pPROM, n=24) and term premature rupture of membranes (tPROM, n=26) according to gestational age. Fifty non-PROM pregnancies matching the same gestational age were recruited as control group. Collagen III CTGF and TNF-alpha in fetal membranes were detected immunohistochemically and analyzed by computer image analysis system. Linear correlation analysis was used to determine the relationship between collagen III, CTGF and TNF-alpha.(1) The expression of collagen III and CTGF in pPROM group (88.81+/-5.25, 85.45+/-6.91) and tPROM group (94.53+/-6.43, 88.15+/-4.93) were decreased significantly (P0.05). (2) The expression level of Collagen III was positively correlated with that of CTGF in pPROM group (r=0.838, P=0.001), but no correlation was found in tPROM group. Collagen III was negatively correlated with TNF-alpha in both pPROM (r=-0.689, P=0.002) and tPROM group (r=-0. 655, P=0.001).Abnormal collagen development caused by CTGF and excess apoptosis of membrane cell caused by TNF-alpha are related to the occurrence of pPROM. However, the basic reason of abnormal collagen resulted in tPROM group is not from CTGF, it may be related with the degeneration of fetal membrane and the TNF-alpha-induced excess cell apoptosis.