At least two calves were killed in the crash.
Shortly before 8 a.m., state police said the truck flipped over on the ramp from northbound I-65 to westbound I-80/94.
The truck was fully loaded with 127 cows, police said. The cows did not get loose. Police set up a pen to get cattle out as they work to upright the truck.
Most of the dairy cattle are now back where they came from at Fair Oaks Farm in Newton County, Indiana.
A spokesperson for the farm said three calves were injured and two of them died.
Cattle truck flips over on expressway ramp in NW Ind.
Indiana State Police said the cattle driver was apparently going too fast when it flipped on its side, blocking all lanes.
Police set up a pen to get cattle out as they worked to flip the truck back over. Crews spent hours cleaning up the scene.
"It's been quite extensive," Indiana State Police Sgt. Glen Fifield said. "There's a large amount of fluid from the truck that leaked out onto the roadways, and vehicles had driven over it. So, the entire area is covered with oil, transmission fluid, stuff like that."
All lanes of I-65 reopened Friday afternoon.
State police said the driver was not injured and was cited for the crash.
"When you have an 80-thousand-pound truck going, taking that curve too fast, it causes problems," Sgt. Fifield said. "We've had a significant number of crashes there over the years. It is posted with warning signs to trucks to slow down."