This study was to investigate the effects of different fractions of Perilla frutescens (Pf) leaves extracted by water or ethanol on asthma. BALB/c mice sensitized intraperitoneally and challenged with ovalbumin (OVA) were divided into six groups. Each group of mice was tube-feeding with 0 (control), 80 μg (PfWL), or 320 μg (PfWH) water extracts or 80 μg (PfEL) or 320 μg (PfEH) ethanol extracts of perilla leaves daily for 3 weeks. A negative control group (PBS) was neither sensitized nor treated with Pf. The effects of perilla leave extracts on allergic immune response were evaluated. The results showed that OVA-specific IL-5 and IL-13 secretions from OVA-stimulated splenocytes were significantly suppressed in the ethanol extract groups PfEL and PfEH. Serum level of anti-OVA IgE tended to be lower in the PfEH group. The inflammatory mediators, such as eotaxin and histamine, and total cells, particularly eosinophils in bronchoalveolar lavage fluid (BALF), were also decreased in the PfEL and the PfEH groups. Therefore, the PfEL and the PfEH groups had significantly lower methacholine-induced hyperresponsiveness (AHR). In conclusion, ethanol extracts, rather than water extract, of perilla leaves could significantly suppress Th2 responses and airway inflammation in allergic murine model of asthma.