Corneal collagen crosslinking is a procedure for making bonds that connect polymer chains. Corneal collagen crosslinking aims to slow or stop the progression of keratoconus by using photooxidative therapy to increase stromal rigidity. This research is aimed to evaluate the effect of transglutaminase-induced corneal collagen crosslinking (CXL) on central corneal thickness and keratocyte cell density in vivo. Twenty-eight white New Zealand rabbits were divided into four groups: the transglutaminase-induced CXL group, the epithelial-off CXL group, the transepithelial CXL group, and the control group. The ocular surface was treated with a 1 U/mL microbial transglutaminase solution, and both the epithelial-off and transepithelial groups were exposed to clinical ultraviolet A-riboflavin (UVA/RF). The efficacy of each group was evaluated on the 14th day after the procedures. Central corneal thickness and keratocyte cell density were evaluated with histopathology examination. Transglutaminase-induced CXL group exhibited the highest mean central corneal thickness (341.10 ± 58.50) in comparison to the UVA/RF epithelial-off group (289.42 ± 38.19), the UVA/RF transepithelial group (319.15 ± 16.81) and control group (318.40 ± 63.97). Still, there was no significant difference, with a p-value of 0.279. Transglutaminase-induced CXL group had the highest mean of keratocyte cell density (43.26 ± 10.65) compared to UVA/RF epithelial-off (29.99 ± 4.79), UVA/RF transepithelial group (42.03 ± 6.55), and control group (34.36 ± 6.76). There was a significant difference between the group, with a p-value of 0.008. It implied that the effect of transglutaminase-induced CXL could be comparable to UVA/RF CXL in altering central cornea thickness and keratocyte cell density.