OBJECTIVE: Extracellular signal-regulated kinase (ERK) is closely related to cellular growth, differentiation and proliferation. This paper aims at (1) detecting ERK1/2 levels in the myocardial cell of viral myocarditis; (2) assessing the effect of ERK specific inhibitor PD98059 on cell viabilities and (3) studying the role of ERK in early viral myocarditis. METHODS: Myocardial cells from neonatal SD rats were incubated in vitro and were randomly assigned into four groups: a Coxsackievirus B3 (CVB3) group, a 20 μmol/L and a 50 μmol/L PD98059 groups and a Control group. CVB3 group was inoculated with CVB3 solutions. The PD98059 groups were initially inoculated with PD98059 for 30 min and then was inoculated with CVB3 solutions. The Control group was treated with DMEM plus 10% FBS. Western Blot was used to detect the ERK 1/2 levels and ERK activation product (P-ERK1/2) levels. Cell viabilities were measured with MTT assay. Cell cytopathic effect (CPE) was used to evaluate myocardial cell lesions. RESULTS: The ERK1/2 levels were not significantly different among the four groups. P-ERK1/2 levels in the CVB3 group were higher than those of the Control group ( 135.57± 0.71 vs 119.41± 1.97; P< 0.01) and also higher than those of the 20 μmol/L and 50 μmol/L PD98059 groups ( 113.75± 1.03 and 42.56± 2.17 respectively; both P< 0.01). P-ERK1/2 levels in the 20 μmol/L PD98059 group were significantly higher those in the 50 μmol/L PD98059 group (P< 0.01). Myocardial cell viabilities of the PD98059 groups ( 0.53± 0.13 and 0.41± 0.04) were higher than the CVB3 group ( 0.17± 0.04) (P< 0.01). There were no differences in myocardial cell viabilities between the two PD98059 groups. Compared with the CVB3 group, myocardial cell lesions in the PD98059 groups occurred later and were less. CONCLUSIONS: CVB3 infection seems to trigger ERK signal transduction pathway. PD98059 may protect myocardial cells from injuries.