Background: Electronic cigarette (E-cig) is a device that instead of burning tobacco leaves evaporates a nicotine solution mixed with liquid tastes. E-cig has been readily available since its introduction in 2004, and its usage has expanded tremendously over the world. This work aimed to compare between the electronic cigarette consumption and tobacco cigarette smoking on urinary bladder, as regard the histopathological effect, oxidative, inflammatory, and apoptotic markers through biochemical and immunohistochemical methods. Forty rats were divided to 4 groups (fresh-air, E-Liquid, E-cigarette, and T-cigarette), after 8 weeks of exposure, rats were weighted and the urinary bladder of all rats were obtained for histological and biochemical analysis. Results: both tobacco and electronic cigarette smoking resulted in a reduction in body weight with increase in urinary bladder weight, an increase in inflammatory marker activity (TNF-α, IL-6, and macrophage inflammatory protein levels), and an oxidant/antioxidant imbalance in rats (increase in ROS level, plus decrease in total antioxidant activity). Furthermore, cigarette smoking caused histological structural injury to the urinary bladder, with overexpression of Ki-67 and poor expression of E-cadherin, all results were more pronounced in tobacco cigarette smoking. Conclusions: According to this study, even if electronic cigarettes have lesser pathological and biochemical effects on the urinary bladder than tobacco cigarettes, they still cause urinary bladder injury, hence it is strongly advised to avoid any devices that contain nicotine.