In this work, the influence of temperature, solvent concentration and ultrasonic irradiation time on viscosity reduction of residue fuel oil (RFO) are studied. The main feature of this research is using ultrasonic irradiation at low frequency of 24 kHz and power of 280W, for viscosity reduction and quality enhancement of RFO. Kinematic viscosity of RFO was found to decrease from 4940 cSt to 2679 cSt due to application of ultrasonic irradiation for 5 min at initial temperature of 20 degrees C. Results showed that combination of ultrasonic irradiation with solvent led to intensified decrease of viscosity and API gravity promotion. The maximum reduction of viscosity (at 133 cSt) occurred in ultrasonic irradiation time of 5 min, temperature of 50 degrees C and acetonitrile loading of 5% by volume. API gravity, distillation and FT-IR analyses revealed that ultrasonic waves have an effective role in cracking and lightening of the examined heavy fuel oil. The measured results including 336 data points of eighty-four samples were analyzed by the feed-forward back propagation of artificial neural network (ANN). The relative importance percent of input variables was calculated and it was found that ultrasonic irradiation time and acetonitrile concentration has maximum and minimum relative importance in viscosity reduction, respectively. (C) 2015 Elsevier B.V. All rights reserved.