The intramammary infusion of xanthosine (XS) has effects on mammary glands in altering stem/progenitor cell population and possibly on milk production. The aim of this study was to evaluate prolong response of XS on stem/progenitor cells, cell proliferation and differentiation and milk production in following lactation in goats. Six primiparous goats were assigned to the study. Twenty milliliters of 10 mM (2 × 3 d) XS was infused 5 d after parturition into one of the randomly allotted gland (TRT) immediately after morning (0900 h) and evening (2100 h) milking. The other gland of the same animal served as control (CON) with no infusion. Mammary tissues were harvested during the dry period (Mean + SE; 136.8 + 11.2 d) and processed for histology. In the next lactation, milk production was recorded until 17 weeks. Immunolocalization of alveolar cell differentiation markers (estrogen receptor α (ESR1), progesterone receptor (PR), mucin 1 MUC1), mammary stem cell markers (nuclear receptor subfamily 5 group A member 2 (NR5A2), aldehyde dehydrogenase 1 (ALDH1), fibronectin type III domain containing 3B (FNDC3B), cell proliferation (Ki67) and apoptosis marker (p53) were quantified in terms of number of immune-positive cells of the total cells counted. XS appeared to enhance expression of NR5A2 (7.7 + 0.9 vs. 4.9 + 0.7; Mann-Whitney U test; z = 0.02) and FNDCB (6.9 + 1.2 vs. 3.1 + 0.3; z = 0.004) in relation to CON glands. Expressions of other markers namely ALDH1, ESR1, PR, MUC1, Ki67 and p53 did not differ between TRT and CON glands. Milk yield (mean + SE) of TRT glands were not different from the CON glands (3462.6 + 156.1 g/wk vs. 3761.3 + 205.8 g/wk; paired t-test P = 0.28). These results suggest XS may have a prolong effects on increasing stem/progenitor cell population during the dry period but has no response in milk production in the next lactation.