Propylene glycol (PG) and glycerol (GL) are common glucogenic supplements for treatment of hyperketonemia or hypoglycemia in sheep. The objective was to determine the diurnal changes (24 h) in blood key metabolites and insulin in response to PG or GL drenching in ewes. Eighteen late-pregnant ewes (~132 d pregnant), averaging 2.97 ± 0.17 BCS, bearing 2–4 fetuses and with blood β-hydroxybutyrate (BHB) concentration of 0.5–1.4 mmol/L were included. Ewes were divided into 3 groups according to BHB levels, expected litter size, BW and BCS, and were drenched with: 1) Control (CTL) – 55 mL of water; 2) PG - 106 mL of PG (448 calories), and 3) GL – 108 mL of Koforin 80 (80% GL; 448 calories). Blood samples were taken before, and post-drenching (PD) every hour for 24 h. Concentrations of glucose, BHB, NEFA, lactate, glycerol and insulin were determined. Data were analyzed using the PROC MIXED procedure of SAS. According to the response pattern, data were analyzed in 3 time-periods PD: (1) 1–6 h; (2) 7–14 h; and (3) 15–24 h. In period 1, glucose concentrations were highest in the GL (P < 0.001), BHB were lowest in the PG (P < 0.001), and NEFA levels were lower in the GL than in the CTL (P < 0.02). Lactate concentrations were highest in the PG (P < 0.0001); glycerol were 5-fold higher in the GL than in the CTL (P < 0.01) and insulin was lower in the CTL than in the GL (P < 0.03). In period 2, glucose concentrations were higher in the PG than in the GL (P < 0.04), BHB were higher in CTL than in GL (P < 0.03), NEFA and insulin were similar, lactate were highest in the PG (P < 0.0004), and glycerol were higher in both PG and GL than in the CTL ewes (P < 0.004). The differences between groups in period 3 were negligible. These results suggest that GL is more effective than PG in enhancing the glucose in the first few hours, but less effective than PG in reducing BHB. In addition, the increased concentrations in lactate in response to PG, and the faster increase in blood glucose in response to GL, suggests on different metabolic path in which these 2 glucogenic precursors enter the gluconeogenesis cycles: PG through lactate and GL through the shortest pathway, which influences the immediate response.