After the dorsal subcutaneous administration of injectable collagen implant derived from bovine dermis (Zyderm; INAMED, Santa Barbara, CA) to mice, ointments that contain 3 types of collagenase inhibitors, Esculetin (6,7-diliydroxy-2H-chromen-2-one), ONO-4817 [(2S,4S)-N-hydroxy-5-ethoxymetliyloxy-2-methyl-4-(4-phenoxybenzoyl) amino-pentanamide], and MMI270 (CGS27023A) {N-hydroxy-2(R)-[(4-methoxysulfonyl)-(3-picolyl)-amino]-3-methylbutanamide hydrochloride monohydrate} were applied daily on the dorsal region of mice (injection site), and intradermal Zyderm was extirpated after 30, 60, and 90 days to measure the level of hydroxyproline. Furthermore, dermal tissue was examined by Azan staining and immunostaining. A significant difference was observed in the level of hydroxyproline in the Esculetin and the ONO-4817 ointment groups compared with that in the control group after 30 days. A significant difference was also observed in the level of hydroxyproline in the Esculetin ointment group compared with that in the control group after 60 and 90 days. Histologically, 90 days after the application of the ointment, dense localization of type III collagen was observed around the injected Zyderm in the group applied Esculetin ointment compared with the control group. Therefore, it was indicated that Esculetin suppressed the degradation of collagen, and further facilitated the qualitative changes that increased neo-collagen, and that the collagen implant with hypodermic injection remained on behalf of ointments contained within the collagenase inhibitors that were applied on the skin surface.