Aging has been reported to increase the risk of developing cerebrovascular disease. Exercise training is well known to have beneficial effects to brain health, including promoted blood flow, angiogenesis and enhanced vascularization. The present study aims to investigate effect of exercise training on age-induced brain microvascular alterations in associated with VEGF and eNOS protein levels. Male Wistar rats were divided into 4 groups: sedentary-young (aged 4-6 months) (SE-Young, n=5), sedentary-aged (aged 23-24 months) (SE-Aged, n= 8), immersed-aged (IM-Aged, n=5) and exercise trained-aged (ET-Aged, n= 8) rats. The study was approved by Ethics Committee on Care and Use of Laboratory Animals, Faculty of Medicine, Chulalongkorn University. ET-Aged rats were individually swum in cylindrical tanks for 60 minutes/day, 5 days/week for 8 weeks. Regional cerebral blood flow (rCBF) was measured by a laser Doppler Flowmeter. Laser-scanning confocal fluorescence microscopy provided high-quality visualization of microvascular network from surface through superficial intraparenchyma. Fluorescent images were recorded and then off-line analyzed for capillary vascularity (CV) by using image analysis software. VEGF and eNOS protein levels in isolated brain microvessels were determined using immunoassay technique. ET-Aged rat was significantly reduced in MAP compared to the IM-Aged group (P<0.05). The rCBF was significantly diminished in SE-Aged (134.99±14.74 PU), IM-Aged (131.09±17.53 PU), and ET-Aged (255.83±13.17 PU) groups when compared to SE-Young group (334.27±35.00 PU). However, the rCBF in the ET-Aged group was significantly higher than that in the IM-Aged group (P<0.05). CV was significantly reduced (P<0.05) in SE-Aged (15.85±1.25%), IM-Aged (16.46±1.59%) and ET-Aged (29.81±1.64%) groups when compared to SE-Young group (39.25±2.18%). The capillary vascularity of ET-Aged group was significantly greater when compared to that of IM-Aged group (P<0.05). The VEGF level was significantly lower (P<0.05) in SE-Aged (20.51±1.75 pg/mg protein) and IM-Aged (19.07±1.27 pg/mg protein) groups compared to SE-Young group (32.27±0.93 pg/mg protein). Swimming training could significant increase (P<0.05) of VEGF level in ET-Aged (28.35±1.53 pg/mg protein) group when compared to that of IM-Aged group. Both SE-Aged and IM-Aged groups have significantly lower (P<0.05) eNOS levels (575.62±70.14 and 459.94±98.02 pg/mg protein, respectively) when compared to SE-Young group (994.39±88.49 pg/mg protein). Regular swimming significantly elevated (P<0.05) eNOS level in ET-Aged group (926.75±65.08 pg/mg protein) when compared with that of IM-Aged group.