Vitamin C (ascorbic acid, AA) is indispensable for normal metabolism of all mammalian cells including pancreatic acinar cells (PAC). PAC obtain AA from their surrounding via transport across the cell membrane. Chronic alcohol exposure negatively affects body AA homeostasis; it also inhibits uptake of other micronutrients into PAC but its effect on AA uptake is not clear. We examined this issue using both in vitro (266-6 cells) and in vivo (mice) models of chronic alcohol exposure. First, we determined the relative expression of the AA transporters-1 & 2 (i. e, SVCT-1 and SVCT-2) in mouse and human PAC and found SVCT-2 to be the predominent transporter. Chronic exposure of 266-6 cells to alcohol significantly inhibited AA uptake, and caused a marked reduction in SVCT-2 expression at the protein, mRNA, and hnRNA levels. Similarly, chronic alcohol feeding of mice significantly inhibited AA uptake and caused a marked reduction in level of expression of the SVCT-2 protein, mRNA and hnRNA. These findings suggest possible involvement of transcriptional mechanism(s) in mediating chronic aclohol effect on AA uptake by PAC. We also observed significant epigentic changes (histone modifications) in the Slc23a2 gene (reduction in H3K4me3 level and an increase in H3K27me3 level) in the alcohol exposed 266-6 cells. These findings show that chronic alcohol exposure inhibits PAC AA uptake and that the effect is mediated, in part, at the level of transcription of the Slc23a2 gene and may involve epigenetic mechanism(s).