Lysyl oxidase (LOX) inhibition prevented volume overload (VO)-induced interstital fibrosis and collagen cross-linking. Animals were divided into the following four groups: sham surgery (sham group), VO surgery (VO) group, sham + LOX inhibitor (β-aminopropionitrile; sham + B group), and VO + LOX inhibitor (VO + B group). The collagen volume fraction (CVF) was calculated from picrosirius red-stained ventricular sections. Representative images are shown. CVF as well as protein measurements of collagen (Col) types I and III were significantly increased in the VO group (A). LOX inhibition completely prevented these increases (A, C, and D). Furthermore, collagen cross-linking was assessed via a pyridinoline assay. Although VO caused a significant increase collagen cross-linking, rats treated with LOX inhibitor had no change in cross-linking (B). n = 4–8 animals/group. Statistical significance is denoted by *P < 0.05 vs. the sham group and †P < 0.05 vs. the VO group.