We examined the expression of outward rectifier K+ channels in activated microglia in vivo. For this purpose, lipopolysaccharide (LPS, 2 microg) was injected into the cortex near the hippocampal region of rat brains, and K+ channel expression was examined using antibodies against shaker-type K+ channels, Kv1.5 and Kv1.3. OX-42-positive microglia were found around the injection sites from 8 h after the LPS injection and remained there for 3 days. The OX-42-positive microglia expressed Kv1.5 immunoreactivity, and the time course of Kv1.5 expression was closely correlated with that of OX-42. In saline-injected brains, OX-42-positive cells also expressed Kv1.5 immunoreactivity even though far fewer OX-42-positive cells were found. Increase of Kv1.5 expression after LPS injection was also demonstrated by immunoblot analysis. On the other hand, Kv1.3 immunoreactivity was barely detected in OX-42-positive cells over the entire experimental period. The expression of Kv1.5 preceded that of inducible nitric oxide synthase (iNOS), which is a prominent indication of microglial activation. iNOS was not detectable until 12 h, and thereafter it was maintained for 3 days together with Kv1.5 and OX-42. These results suggest that in vivo as well as in vitro activated microglia expressed outward K+ channels and that some of the channels at least are Kv1.5.