Rosiglitazone, a PPARγ thiazolidinediones (TZDs) agonist, has been proposed to have neuroprotective effects in the central nervous system (CNS). However, the mechanisms underlying the beneficial effects of rosiglitazone are unclear. In the present study, primary cultured hippocampal neurons of 1-day-old wistar rats were transfected with farnesylated enhanced green fluorescent protein (F-GFP) and GFP-actin on day 5 in vitro (DIV5) to display the morphological details of the dendrites and dendritic protrusions. Different doses of rosiglitazone (5, 10 and 20 μmol/L) or 20 μmol/L rosiglitazone with the presence of 5 μmol/L GW9662, an antagonist of PPARγ, were applied to neurons for 24 h at DIV6. Live-cell imaging technology was used to investigate the effects of rosiglitazone on the development of dendritic filopodia and dendritic tree in hippocampal neurons at DIV7. Our results have shown that rosiglitazone increased the density of dendritic filopodia in a dose-dependent manner. The filopodia density of cultured neurons in 10 μmol/L ((34.27 ± 2.12)/100 μm, n = 21) and 20 μmol/L ((37.75 ± 2.09)/100 μm, n=21) rosiglitazone treated group was significantly increased compared with those of control group((26.45±1.47)/100 μm, n=21), but the filopodia density of cultured neurons in 5 μmol/L rosiglitazone treated group ((27.66 ± 1.84)/100 μm, n=20) was not significantly altered compared with those of control group. Rosiglitazone treatment of 5, 10 and 20 μmol/L concentrations has no effect on the length and motility of dendritic filopodia. In addition, neither the length nor the number of dendritic branches was altered by treatment of 5, 10 and 20 μmol/L rosiglitazone. 5 μmol/L GW9662 attenuated the increased filopodia density induced by 20 μmol/L rosiglitazone. These results suggest that rosiglitazone may affect the initial stage of hippocampal neuron development through the PPARγ pathway. This may be a possible mechanism of the neuroprotective effects of rosiglitazone.