PURPOSE: The intramuscular route (IM) is widely used but commonly induces injection site muscle damage. This study investigates the hemodynamic changes in an acute lesion induced by the IM administration of propylene glycol (PG) in rabbits. METHODS: Control groups received 1, 2, or 3 ml of PG (IM). Others were pretreated with pancuronium, dantrolene, indomethacin, or SR140333 and then received 2 ml of PG. The muscle blood flow (MBF) was assessed using fluorescent microspheres before and at 15, 45, 60, 90 min, 3 and 6 h after IM administration. Different areas within the muscle damage were quantified. RESULTS: Muscle contractions as well as a transient but major MBF increase were observed at the injection site. All treatments reduced hyperemia by up to 81% (dantrolene, 15 min) at 15, 45, and 90 min (p < 0.05). MBF had returned to basal values in all groups at 6 h. The central necrotic area was not modified, but peripheral damage (8.0 +/- 1.3 g) was reduced by dantrolene, indomethacin, and SR140333 (p < 0.05), but not by pancuronium. CONCLUSIONS: Muscle contraction and hyperemia are not responsible for muscle damage at the injection site, which is the multifactorial phenomenon, involving intracellular calcium and inflammation.