The optical clearing technique has shown great potential in improving light penetration into biotissues. Among various optical clearing agents (OCAs) under study, the hydroxyl-terminated agents induce the highest optical clearing effect of skin, but the exact mechanism of optical clearing is still unclear. In consideration of several probable factors, such as the number of hydroxyl groups, the refractive index, and the molecular weight, we investigate the optical clearing effect of porcine skin after applying six alcohols to the epidermis and saline to the dermis. The dynamical transmission intensity of porcine skin is monitored by an integrating sphere system, and the thickness of skin samples is measured before and after experiments. The results show that the transmittance of skin increases significantly, but there is no significant change in thickness after the treatment of OCAs. The optical clearing effect of skin induced by alcohols is related to the number of hydroxyl groups. The refractive index or molecular weight of optical clearing agents does not correlate with the degree of optical clearing effect for a 60-min time interval of measurement. However, the behavior of skin transmittance after 60 min needs to be further investigated.