An ultrasensitive immunosensor based on acetylene black (AB)/epoxy-substituted-poly(pyrrole) polymer (EpxSPPyr) composite coated disposable indium tin oxide (ITO) electrode was fabricated for interleukin 6 (IL 6) detection. The EpxS-PPyr polymer was a promising matrix material to increase the loading capacity of immunosensor owing to its large surface area and abundance of epoxy groups. EpxS-PPyr polymer was synthesized by an esterification reaction and used to attach IL 6 receptor owing to its excellent biocompatibility and good conductivity. The electrochemical signals of the electrodes during the immunosensor fabrication were performed with electrochemical impedance spectroscopy and cyclic voltammetry techniques. Additionally, the changes formed on ITO electrode surfaces were followed by scanning electron microscopy and atomic force microscopy analyses. Under optimized conditions, the designed biosensor illustrated an ultra-sensitive signal towards IL 6 antigen at a broad concentration range from 0.01 pg/mL to 50 pg/mL. The detection limit and sensitivity were found as 3.2 fg/mL and 0.29 pg(-1)mLk Omega cm(-2), respectively. Acceptable reproducibility, good storage-stability and excellent selectivity were found for IL 6 determination. Moreover, the proposed biosensor was applied to human serums and the recovery rates were ranged from 99.5 to 100.5 indicating acceptable accuracy. The results illustrated that this immunosensor were suitable for detection of IL 6 in clinical samples.