The activation of peroxisome proliferator-activated receptor γ (PPAR-γ) has been shown to attenuate allergic airway inflammation (AAI). To gain better understanding of mechanisms underlying this effect, the impact of rosiglitazone (RSG), a PPAR-γ agonist, on CD4 effector (Teff) and Foxp3-expressing regulatory (Treg) T cells in a mouse model of allergic asthma was studied. Furthermore, we investigated whether the activation of PPAR-γ may directly affect IL-4, IL-10 and IL-17 production by CD4 T cells. RSG attenuated but did not prevent ovalbumin (OVA)-induced AAI, and this effect was PPAR-γ-dependent. RSG reduced but did not abolish the OVA-induced increase in the count of CD4 Teff cells in the mediastinal lymph nodes (MLNs) and lungs, and this effect was PPAR-γ-dependent. RSG did not affect the absolute number of Treg cells in the MLNs and lungs of OVA-immunized mice. In vitro exposure of lung lymphocytes to RSG did not influence the percentage of IL-4-, IL-10- and IL-17-producing CD4 T cells. Our results indicate that the impairment of clonal expansion of CD4 Teff cells in the MLNs is involved in the anti-asthmatic properties of PPAR-γ agonists. Activation of PPAR-γ did not affect the recruitment of Treg cells to the MLNs and lungs nor did it induce their local generation. This indicates that Treg cells are not involved in producing the anti-asthmatic effect of PPAR-γ agonists. The results suggest that beneficial effects of PPAR-γ agonists in asthma treatment are not mediated through a direct inhibitory effect on IL-4, IL-10 and IL-17 production by CD4 Teff cells.