HPC-1/syntaxin 1A (STX1A) is abundantly expressed in neurons. STX1A is believed to regulate exocytosis in synaptic vesicles. In our recent studies, STX1A knockout (KO) mice showed normal development, and basal synaptic transmission in cultured hippocampal neurons appeared to be normal. However, behavioral abnormalities were observed in STX1A KO mice. In the normal rodent retina, the STX1A protein is expressed in two synaptic layers (plexiform layers). Here, to evaluate the effects of the loss of STX1A on retinal structure, we examined the retinal layer structure in STX1A KO mice using hematoxylin staining and immunostaining. We found that the general layer structures in the retina were preserved in all genotypes. However, the outer plexiform layer (OPL) was significantly thicker in KO and heterozygous mutant (HT) mice compared with that in wild-type (WT) mice. No significant differences were observed in the thicknesses of the other layers. Immunostaining for protein kinase C alpha showed that the alignment of rod bipolar cell bodies in the inner nuclear layer (INL) was slightly disrupted in HT and KO retinas. Furthermore, the dendrites of these cells in the OPL of KO mice were sparse, compared to those in WT mice. Our results show that STX1A KO mice have increased thickness of the OPL and changes in the morphology of the INL that may contribute to the change in OPL thickness. We suggest that STX1A may play a role in the structural formation of the INL and OPL in the retina.