In a previous study, we found that the effect of drenching late-pregnant prolific ewes with propylene glycol (PG; 106 mL) or glycerol (GL; 108 mL) was different; while PG was anti-ketogenic, the effect of GL was mainly glucogenic. In the present study, the effect of different doses of PG and GL was examined in late-pregnant ewes (~132 d pregnant) bearing 2–4 fetuses. Thirty ewes were divided according to BHBA blood levels, expected litter size, BW and BCS into 5 groups (6 ewes each) and were drenched with: 1) Control - 55 mL water; 2) PG100 - 106 mL PG; 3) GL100 - 108 mL GL (80%); 4) PG50 - 53 mL PG; 5) GL50 - 54 mL GL (80%). Blood samples were taken 60 and 30 min before, and every hour post-drenching (PD) for 13 h. Concentrations of glucose, BHBA, 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 2 time-periods PD: 1) 1- 6 h; 2) 7 - 13 h. During period 1, glucose and insulin concentrations were higher in GL100 than in other groups (P < 0.05); PG50 was more effective in reducing the BHBA concentrations than PG100 with no differences in NEFA concentrations. Lactate concentrations were similar between PG100 and PG50, but higher than other groups (P < 0.02). Further, we tested the effects of mixtures of both substances in a similar design and analysis. Eighteen ewes were divided into 3 groups, and were drenched with: 1) Control - 55 mL of water; 2) MIX100 - 53 mL PG + 54 mL GL (80%); 3) MIX50 - 26.5 mL PG + 27 mL GL (80%). No differences were observed in glucose, BHBA, NEFA, glycerol and insulin concentrations between groups in both periods; however, lactate concentrations were higher in the MIX100 group at period 1 (P < 0.05). In conclusion, in a few parameters, lower doses of both substances seemed to be more effective than higher doses. In addition, mixtures of PG and GL were not effective in achieving the anti-ketogenic and glucogenic effects simultaneously. The results of this study showed that further research is required to establish proper doses and composition of these substances.