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It was shown that the concept of drag-reducing in the pipe flow with the aid of macromolecules is of great importance in practical engineering applications. In this study, the drag-reducing the performance of three biological macromolecules including guar gum (GG), xanthan gum (XG), and carboxymethyl cellulose (CMC) was compared with three synthetic macromolecules including polyethylene oxide (PEO), polyacrylamide (PAM), and polyacrylic acid (PAA). Results showed that all the macromolecules enhanced the DR% except for GG. DR% for almost all of the macromolecules deteriorated with increasing fluid flow rate. On the other hand, DR% enhanced with increasing the pipe diameter for the synthetic polymers but this effect is not obvious for biological polymeric solutions. Maximum DR was 44%, which occur at 1000 ppm concentration of XG at 30 °C and flow rate of 6 l/min and diameter ½ inch. Finally, a new correlation was developed for the prediction of friction coefficient based on the Prandtl-Karman relation with the newly adjusted slope which is a linear function of polymer concentration. This correlation was in excellent agreement with the experimental data.