Anal fissure (AF) is one of the most common anorectal problems. The severity of the disease, the chronicity of the pathological process and frequent complications lead to a sharp deterioration in the quality of life of patients. An important place in the treatment of anal fissure is occupied by drugs that affect its key mechanism of pathogenesis, namely, reduce the muscle tone of the internal anal sphincter and have anti-inflammatory, analgesic, and reparative properties. Aim: conducting of screening studies of the effectiveness of new test samples of rectal cream of the combined composition (RCCC) on the model of acute complicated anal fissure in rats and determining the optimal composition of the potential drug. Materials and methods. The research was conducted on the basis of the Central Scientific Research Laboratory of the National Pharmaceutical University (CSRL NUPH) in the spring (April) season of 2015 on the female rats. A study of test specimens of the rectal cream of the combined composition was performed on a modified model of acute anal fissure. The effectiveness of the treatment was evaluated in terms of (0 to 2) severity of edema, hyperaemia, local bleeding, purulent necrotic processes, scapular formation, anatomical defect, and a general indicator of the severity of the pathological process (by the sum of the points for all the criteria that were analyzed). The level of proinflammatory PGE2 in serum was determined by the immune enzyme method. Results. The RCCC sample No. 4 showed the most expressive therapeutic effect among the four samples under study, and had credible benefits to the inhibitory effect on purulent-necrotic processes, as expressed by the differences in the overall rate of the pathological process (6 days: 5.83±0.47 points against 7.00±0.37; 7.83±0.31 under the influence of RCCC No. 2, No. 3, respectively, and for 11 days 5.00±1.03 versus 6.83±1.28 points (p=0.08 ) under the influence of RCCC No. 1). The ability of RCCCs No.1 and No.4 to reduce the level of pro-inflammatory PGE2 in blood serum of rats compared with CP in 1.8 and 2.0 times, respectively, contributed to accelerating epithelization and scar formation. The advantages of RCCC No. 4 on the comparison of the ointment "Proctozan" with the reduction of the period of epithelization of the defect of the mucous membrane of the anal canal for 3 days (for 7 days – RCCC No. 4, for 10 days - ointment "Proctozan"). Conclusions. The rectal cream of the combined composition No. 4 showed the greatest efficacy, had advantages over the comparison ointment "Proctozan", and is promising for the creation on its basis a new drug for the treatment of anal fissures.