The aim of this study was to investigate the crosslinking effect of lysyl oxidase (LOX) alone and in combination with genipin (GNP) on the sclera of myopic eyes. A total of 116 guinea pigs were used in this study. Among them, 16 guinea pigs were used as normal controls. The others were established as a lens-induced myopia model. The study included 80 guinea pigs with myopia higher than -6.0D. There were 12 groups of guinea pigs (A-L). Groups A and B included guinea pigs with normal eyes treated with saline and 0.1% LOX, respectively. Groups C, D, E, F, G, H, I, J, K, and L had myopic eyes. Groups C, D, E, and F were treated with saline, 0.1% LOX, 0.5% LOX, and 1% LOX, respectively. Groups G, H, and I were treated with 0.1% LOX + 1% GNP, 0.5% LOX + 1% GNP, and 1% LOX + 1% GNP, respectively, and allowed to react for 4 h. Groups J and K were treated with 1% LOX + 1% GNP for 8 h and 12 h, respectively. Group L was treated with 1% GNP for 4 h. The biomechanical features and fixation index of crosslinking between the groups and among 16 eyes in each group were compared. The isolated sclerae were treated with various agents in vitro. The elastic modulus and tensile strength of the sclerae were measured in 10 eyes from each group using an electronic microtensile machine. Samples from the other six eyes of each group were used to determine the fixation index via a ninhydrin assay. Significant differences were observed in the elastic modulus and tensile strength measurements between groups A (saline) and B (0.1% LOX) with normal eyes (P < 0.05), between groups C (saline) and D (0.1% LOX) with myopic eyes (P < 0.05), and between group C (saline) and groups D (0.1% LOX), E (0.5% LOX), and F (1% LOX) (P < 0.01). However, there were no differences among groups D, E, and F (P > 0.05). Moreover, there were significant differences among groups I (1% LOX + 1% GNP, 4 h), J (1% LOX + 1% GNP, 8 h), and K (1% LOX + 1% GNP, 12 h) (P < 0.05). There was a significant difference in the mean elastic modulus between group L (1% GNP) and groups F (1% LOX) and I (1% LOX + 1% GNP) (P < 0.01), but there was no difference between group F and group I (P = 0.412). LOX had a crosslinking effect on the sclera of normal as well as on myopic eyes. The effect of crosslinking of LOX was weaker than that of GNP, and no catalytic crosslinking effect of LOX was shown with GNP in the present study. [ABSTRACT FROM AUTHOR]