Objective To investigate the expressions of interleukin (IL)-21 and phosphorylated extracellular signal regulated kinase 1/2 ( pERK1/2) in Kimura disease (KD) and to correlate the findings with clinical and prognostic variables. Methods Immunohistochemical analysis of IL-21 and pERK1/2 was performed in 18 cases of KD and five gender-and age-matched control samples. Clinical data were extracted and patients followed up for a mean period of 32.1 months.Results After a mean follow-up period of 32.1 months (range 1-102 months), recurrence was diagnosed as the end point for seven patients-that is, a 44% (7/16) cumulative recurrence rate. In comparison with genderand age-matched controls, patients showed strong in situ expressions of IL-21 and pERK1/2, respectively ( p<0.05). Patients with strong IL-21 staining intensity and overexpression of pERK1/2 had a lower recurrence rate than those with moderate staining intensity ( p=0.049, p=0.019, respectively). However, differences were not statistically significant by gender, age, eosinophils, location, multiplicity, laterality, size, duration and primary outbreak. pERK1/2 was the independent prognostic factor ( p=0.020), while age, gender, eosinophils, multiplicity, laterality, size, duration, primary outbreak and expression of IL-21 were not. Conclusions This study suggests that the IL-21/pERK1/ 2 pathway is activated in KD, and pERK1/2 might be considered as a potential prognostic indicator in KD.