Cystic endometrial hyperplasia-pyometra complex is a canine endometrial disorder, considered the most common and important among uterine diseases. The treatment of choice is ovariohysterectomy, but medical treatments have become an alternative. However, no studies have been performed in order to evaluate uterine hemodynamic changes during medical treatment for pyometra bitches. Therefore, the aim of this study was to compare the effectiveness of two medical protocols by means of clinical (heart rate, respiratory rate and body temperature), medullar response (complete blood count (CBC)) and uterine hemodynamic evaluation in pyometra bitches. For such purpose, 10 bitches with pyometra were assigned to two groups: Aglepristone Group (n = 5) and Associative Group (aglepristone + prostaglandin; n = 5). The Associative Group had altered respiratory rate and decreased body temperature. The Aglepristone Group had decreased plasma protein, however, leukocyte count reduced over time for both therapeutic protocols. Uterine area and vascularization score decreased throughout treatment. There was a significant reduction in uterine perimeter, area and vascularization score. The Associative Group had lower final diastolic velocity and higher systole:diastole ratio (S/D), pulsatility index (PI) and resistance index (RI). In conclusion, both medical treatments are effective in reversing clinical and CBC changes of pyometra, especially aglepristone, however they cannot fully restore local uterine changes in a short-term evaluation. Conversely, associative therapy was more effective in decreasing uterine vascularization and modulating uterine blood flow.