Human Immunodeficiency Virus (HIV) is known to bind CD4 receptor and subsequently to CXCR4 or CCR5 coreceptors and further transmits the infection. However sperm and vaginal epithelial cells which are known to be responsible for sexual transmission of HIV are devoid of conventional CD4 receptor. HIV has been demonstrated to bind human Mannose Receptor (hMR) and enter into sperm to transmit the virus into distal cells. Subsequent studies by immunofluorescent and Real time PCR techniques demonstrated specific binding of HIV to hMR on Vaginal epithelial cells also. Further peri-ovulatory expression of hMR on vaginal epithelial cells was found to be higher as compared to that during pre and post ovulatory period. HIV binding to hMR on vaginal epithelial cells leads to increase production of Matrix Metallo-Proteinases 9 (MMP9) which may be responsible for viral entry into the cells by inducing the cellular permeability. It was observed that less than 11% of the vaginal epithelial cells of the HIV negative females having unprotected sex with their infected sexual partners showed the presence of hMR. While 90 to 95% of vaginal epithelial cells HIV negative women from general population showed the presence of hMR. This suggests that the expression of hMR in lower number of vaginal epithelial cells protected these females from sexual transmission of HIV from their HIV infected partners. The study suggests the association of hMR in sexual transmission of HIV.