We have previously shown that hyaluronan (HA) and its receptor RHAMM(Receptor for HA-Mediated Motility) regulate macrophage motility during bleomycin-induced pulmonary inflammation. Since steroid therapy has been used to limit inflammation in this model, and may limit the severity of bronchopulmonary dysplasia in premature infants, we hypothesized that, in addition to reducing the inflammatory response, steroids would reduce the expression of RHAMM and HA after bleomycin-induced lung injury in rats. Sprague-Dawley rats (n=5/group) were treated with either 30 mg/kg solumedrol intramuscularly (IM), or 1 mg budesonide intratracheally (IT) 1 day prior to and daily for 4 days after intratracheal bleomycin. Control animals received an equal volume of normal saline by the same routes. Four days after injury, bronchoalveolar lavage (BAL) was performed. The cells from the BAL were separated from the lavage fluid by centrifugation. The HA content of the lavage fluid was measured using an ELISA-like assay, while the cells were analyzed for RHAMM content by western blot, and macrophage content by glucosaminidase activity. Steroid treatment decreased HA content of the lavage fluid by 40%, and decreased RHAMM expression by 40% (IM) and 90% (IT) as compared to controls. Both treatments resulted in a 40% reduction in macrophage accumulation in the lungs of injured animals. We conclude that, in addition to decreasing pulmonary inflammation after intratracheal bleomycin, steroids decrease the expression of RHAMM and HA in vivo. We speculate that the anti-inflammatory action of steroids in lung injury may be explained in part by the inhibition of RHAMM and HA.