It happened just before 3:40 p.m. on eastbound Interstate 80 in Joliet, approximately 40 miles from Chicago.
According to Illinois State Police, a cattle hauler carrying 33 cows went off the road and struck a disabled semi-trailer.
After the cattle hauler hit the semi, it continued on to strike a white Honda coupe, with an 82-year-old man inside, before splitting open and throwing about 16 cattle onto the interstate, according to ISP.
The driver of the cattle hauler was identified as 51-year-old Bradley E. Pate of Waynesboro, Virginia.
State police have charged Pate with driving under the influence of drugs. He was also issued a citation for failing to reduce speed to avoid an accident and improper lane usage.
Police say Pate was taken to a local hospital with life-threatening injuries.
The 82-year-old man was taken to the hospital with non-life-threatening injuries.
The driver of the semi-truck was not injured.
State police said four cows died in the crash. Two had to be put down due to injuries, one died in the road and one died in the hauler.
With the help of local farmers on horseback, the remaining cattle were gathered up and hauled away to a local storage location, police said.
The eastbound lanes of the roadway were shut down for close to six hours.