This study was designed to investigate the effect of recombinant human endostatin (YH-16) combined with oxaliplatin (L-OHP) on the growth of orthotopically-implanted human colorectal carcinoma in nude mice. Tumour volumes and weights were measured after therapy. Tumour cell morphology was observed by light and electron microscopy. Apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) assay, and vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) were determined by immunohistochemical staining. Tumour volumes in all treatment groups were significantly reduced compared with controls. YH-16 and L-OHP either alone or in combination caused tumour cell apoptosis, except in the YH-16 low-dose group. MVD was strongly inhibited in the treatment groups compared with the controls, although only YH-16 combined with L-OHP or L-OHP alone decreased VEGF expression. No obvious change in side-effects occurred. In conclusion, YH-16 combined with L-OHP inhibited growth and induced apoptosis in orthotopically-transplanted human colorectal carcinoma in nude mice without increasing side-effects.