The hypothesis that thrombus can be induced by localized shear stresses/rates, such as in the bent/stretched microvessels, was tested both experimentally and computationally. Our newly designed in vivo experiments were performed on the microvessels (post-capillary venules, 20-50 microm diameter) of rat mesentery. These microvessels were bent/stretched with no/minimum injuries. In less than 60 min after the microvessels were bent/stretched, thrombi were formed in 19 out of 61 bent locations (31.1%). Interestingly, thrombi were found to be initiated at the inner wall of the curvature in these bent/stretched vessels. To investigate the mechanical mechanisms of thrombus induction, we performed a 3-D computational simulation using commercial software, FLUENT. To simulate the bending and stretching, we considered the vessels with different curvatures (0 degrees , 90 degrees and 180 degrees ) as well as different shaped cross-sections (circular and elliptic). Computational results demonstrated that the highest shear stress/rate and shear stress/rate gradient are located at the inner wall of the curved circular-shaped vessels. They are located at the two apexes of the wall with shorter axis for the 0 degrees (straight) elliptic-shaped vessel and towards the inner side when the vessels are bent. The differences of the shear stresses/rates and of the shear stress/rate gradients between the inner and outer walls become larger in more bent and elliptic-shaped microvessels. Comparison of our experimental and numerical simulation results suggests that the higher shear stress/rate and the higher shear stress/rate gradient at the inner wall are responsible for initiating the thrombosis in bent post-capillary venules.