The hepatic response to cyclic adenosine monophosphate (cAMP) and N6-monobutyryl-cAMP (N6-MB-cAMP) in the glucose and glycogen catabolism and hepatic glycogen levels were evaluated in Walker-256 tumor-bearing rats, on days 5 (WK5), 8 (WK8), and 11 (WK11) after the implantation of tumor. Rats without tumor fed ad libitum (fed control rats) or that received the same daily amount of food ingested by anorexics tumor-bearing rats (pair-fed control rats) or 24 h fasted (fasted control rats) were used as controls. Glucose and glycogen catabolism were measured in perfused liver. Hepatic glycogen levels were lower (p < 0.05) in WK5, WK8, and WK11 rats in comparison with fed control rats, but not in relation to the pair-fed control rats. However, the stimulatory effect of cAMP (3 and 9 μM) in the glycogen catabolism was lower (p < 0.05), respectively, in WK5 and WK8 rats compared to the pair-fed and fed control rats. Accordingly, the suppressive effect of cAMP (6 μM) in the glucose catabolism, under condition of depletion of hepatic glycogen (24 h fast), was lower (p < 0.05) in WK5 and WK11 rats than in fasted control rats. Similarly, the suppressive effect of N6-MB-cAMP (1 μM), a synthetic analogue of cAMP that it is not degraded by phosphodiesterase 3B (PDE3B), in the glucose catabolism was lower (p < 0.05) in WK5 rats compared to fasted control rats. In conclusion, livers of Walker-256 tumor-bearing rats showed lower response to cAMP in the glucose and glycogen catabolism in various stages of tumor development (days 5, 8 and 11), which was probably not due to the lower hepatic glycogen levels nor due to the increased activity of PDE3B.