We investigated the activation and cellular distribution of two signaling pathways, the signal transducers and activators of transcription (STATs) and mitogen-activated protein kinases (MAPKs) following kainic acid (KA)-induced seizures, in relation to the expression of gp130, a common cytokine signal transducer for the interleukin (IL)-6 family of cytokines. Rapid and short-lasting upregulation of gp130 was observed in the granule cells. This became evident in astrocytes by 3 h, increased progressively to peak at 3 days, and was sustained for 10 days. STATs, including STAT1 and STAT3, and p42/44 MAPK were activated in distinct cellular and spatial distributions within the hippocampus following seizures. A rapid and sustained seizure-induced activation of STAT3 and STAT1, revealed by nuclear STAT3 and STAT1 immunoreactivities, was observed exclusively in reactive astrocytes in the hippocampus, nearly coinciding with the time course of gp130 expression; however, STAT3 activation was greater. In contrast, seizure induced the rapid and transient activation of p42/44 MAPK in a subpopulation of hippocampal neurons and in astrocytes, although with weaker staining intensity. Two signaling pathways involving gp130, STATs and MAPK, were differentially activated in reactive astrocytes after KA injection, indicating that STATs and MAPK may differentially mediate the astroglial reaction in the rat hippocampus after KA-induced seizures.