The pituitary gland contains a complex portal system that transfers signals from the pars tuberalis (PT) and infundibulum to the pars distalis (PD). Vascular loops arising from the PT, traverse to the infundibulum, an area encompassing glial cells and endothelium in close proximity, before descending towards the PD as long portal vessels. Vascular endothelial growth factor (VEGF), originally isolated from the pituitary gland, has been identified as a key regulator of endothelial function, controlling angiogenesis and vascular permeability, the latter via regulation of fenestrations. We hypothesised that VEGF-mediated remodeling of pituitary microvasculature may therefore play a role in the control of reproductive function by acting to either maintain, remodel or signal through this vasculature. If this was the case, one would expect the functional remodeling of this microvasculature to be under seasonal regulation in photoperiodic species as a key mechanism underlying the control of temporal changes in seasonal fertility. To test this hypothesis, pituitary glands from adult ewes were collected during the breeding season (BS; n=5) and non-breeding season (NBS; n=5). The expression of pro- (VEGFxxx) and anti- (VEGFxxxb) angiogenic isoforms was revealed in PT cells co-expressing the melatonin receptor MT1-R, endothelial cells of the vascular loops, and both glial and endothelial cells of the infundibulum. Seasonal variation in VEGF isoform expression was observed in the PD, with a significantly higher content of the anti-angiogenic VEGFxxxb during the BS (p<0.01), and an increase in the expression of angiogenic VEGFxxxa (p<0.01) during the NBS. Consistent with these findings, total cell proliferation and endothelial cell proliferation were both significantly increased in the PD during the NBS (p<0.01). In contrast, no such seasonal changes of VEGF expression or cell proliferation were detected in the PT (p>0.05). The expression of S-100, a marker of folliculo-stellate cells (FSC) known to produce VEGF, was significantly increased during the NBS in the PD (p<0.01), where expression of VEGFR2 by lactotrophs, endothelial cells, FSC and other endocrine cells was also observed. Critically, seasonal alterations to the intrinsic morphology of the vascular loops of the infundibulum were also identified. The number and area of these loops were significantly increased during the NBS (p<0.05). These findings support a role for VEGF-mediated pituitary vascular remodeling in the mechanisms underlying the pituitary control of temporal changes in fertility.