To study the effect of organic Se on spatial learning and memory deficits induced by Pb exposure at different developmental stages, and its relationship with alterations of synaptic structural plasticity, postnatal rat pups were randomly divided into five groups: Control; Pb (Weaned pups were exposed to Pb at postnatal day (PND) 21–42); Pb-Se (Weaned pups were exposed to Se at PND 43–63 after Pb exposure); maternal Pb (mPb) (Parents were exposed to Pb from 3 weeks before mating to the weaning of pups); mPb-Se (Parents were exposed to Pb and weaned pups were exposed to Se at PND 43–63). The spatial learning and memory of rat pups was measured by Morris water maze (MWM) on PND 63. We found that rat pups in Pb-Se group performed significantly better than those in Pb group ( p <0.05). However, there was no significant difference in the ability of spatial learning and memory between the groups of mPb and mPb-Se ( p >0.05). We also found that, before MWM, the numbers of neurons and synapses significantly decreased in mPb group, but not in Pb group. After MWM, the number of synapses, the thickness of postsynaptic density (PSD), the length of synaptic active zone and the synaptic curvature increased significantly in Pb-Se and mPb-Se group; while the width of synaptic cleft decreased significantly ( p <0.05), compared to Pb group and mPb group, respectively. However, the number of synapses in mPb-Se group was still significantly lower than that in the control group ( p <0.05). Our data demonstrated that organic Se had protective effects on the impairments of spatial learning and memory as well as synaptic structural plasticity induced by Pb exposure in rats after weaning, but not by the maternal Pb exposure which reduced the numbers of neurons and synapses in the early neural development.