In the present study we investigated the effects of glucocorticoids (GC) and methylphenidate (MPH) on SHR’s behavioral feature and expression of glucocorticoid receptor (GR) in the prefrontal cortex. At 3 weeks of age, all animals except controls were given either MPH (4 mg/kg.d), Dexamethasone [DEX, (0.5 mg/kg.d)], or Mifepristone [RU486 (54 mg/kg.d)] for 2 weeks. Behavior feature were evaluated by open field test and LAT maze test before and after intervention. Immunohistochemical technique was used to assess the expression of GR. Additionally, effects of GC-KLF11-MAO pathway on the expression of monoamine oxidase A (MAOA) and effects of MPH on the pathway were investigated in primary cultured neurons of SD rats. The expression of KLF11 and MAOA was detected by immunocytochemistry technique. Results revealed decrease of hyperactivity and inattention displays after MPH or DEX intervention (P<0.05). GR expression in MPH (0.242±0.102) and DEX group (0.230±0.001) were both higher when compared with CON group (0.158±0.044) (P<0.05). As analyzed by linear regression, hyperactivity and inattention features of SHR in LAT maze test and open field test were all negatively correlated with GR expression levels(P<0.05). Comparing to CON group, both KLF11 (0.139±0.01) and MAOA (0.143±0.01) expression were higher (0.108±0.01, 0.123±0.00) after GC intervention (P<0.05). MAOA (0.112±0.01) expression was lower after RU486 administration when compared with CON group. However, RU486 administration did not decrease KLF11 (0.124±0.00) expression (P<0.05). MPH treatment did not showe effect to KLF11 (0.112±0.01) and MAOA (0.123±0.00) expression (P>0.05).