Two rabies post-exposure therapies were comparatively evaluated: BALB/c mice were challenged at day 0 with rabies virus and then received either a single dose of rabies DNA vaccine administered at day 0, or five doses of cell culture-derived rabies vaccine administered at days 0, 3, 7, 15 and 28. Both regimens, rapidly triggered protective levels of neutralizing antibodies against rabies virus in vaccinated mice. In addition, one injection of DNA vaccine protected 53% of the challenged mice, compared to 40% of mice protected after five injections of cell culture-derived vaccine. We conclude that rabies post-exposure vaccination in BALB/c mice, based on a single administration of rabies DNA vaccine might be at least as effective as five injections of cell culture-derived vaccine.