Mechanism underlying Chlamydia trachomatis disease pathology is not completely understood. It was hypothesised that dysregulation of extracellular matrix by matrix metalloproteinases (MMPs) might be involved in sequelae of events leading to abortion in C. trachomatis-infected women. Hence, this study was undertaken to elucidate the expression of MMP-2/MMP-9/TIMP-1/TIMP-3 in infected recurrent spontaneous aborters (RSA) and simultaneously ascertain effect of few cytokines (TNF-α, TGF-β1, TGF-β2)/cyclooxygenase-2 (Cox-2) on MMPs. Endometrial curettage tissue was collected from 135 RSA (group I) and 120 age-matched controls (group II) at Department of Obstetrics and Gynecology, SJH, New Delhi (India). PCR was performed for diagnosis of C. trachomatis MOMP/plasmid gene. Expression of MMP-2/MMP-9/TIMP-1/TIMP-3 mRNA was assessed by quantitative real-time PCR. Data were statistically evaluated. 15.6% (n = 21) RSA (Group-I) were diagnosed as C. trachomatis positive. Significant upregulation of MMP-2/MMP-9 and decreased TIMP-1/TIMP-3 were found in C. trachomatis-positive RSA (group I) versus control women (group II). MMP-2 was found positively correlated with cytokines/Cox-2. Significant positive correlation was observed between MMP-2/MMP-9 and C. trachomatis copy load. Overall data suggested that dysregulated MMPs/TIMPs promoted excessive endometrial matrix degradation which, in turn, affected pregnancy leading to spontaneous abortion in infected women.