Smoke filled the sky from the TA Truck Stop at Russell, Miss., three miles east of Meridian around 12 noon Friday.
A construction crew was working on the roof of an addition to the building when an apparent chemical reaction started the blaze.
"They were putting a roof on a part of the new construction they were doing here and the best we can tell they had a chemical reaction that ignited the fire. Two or three people were burned," said Clarence Butler, director of Lauderdale Emergency Management Agency.
Three employees of Cross Roofing were transported to Meridian hospitals with varying levels of injuries.
"I came around the fuel pumps and there was a gentleman covered in smoke. I mean the smoke-steam was coming off him. Somebody had grabbed a hose and begun to put him out," said Diana Roepcke, who happened to be arriving around the time the fire started and is a trained first responder.
One man was severely burned over most of his body, another sustained injuries when he leaped off the roof to escape the fire.
"He was on the ground and it looked like he was burned on most of his body, his face and his arms and his legs, and I guess another individual had jumped out of the building and injured his back," Roepcke said.
Officials suspect the fire started when the two parts of the roofing adhesive were mixed, resulting in very high heat.
"We really don't know exactly, but they told us they were using a rubber-based material for the roof up there and of course the chemicals that make that stuff heat up and bond together evidently caused a chemical reaction to start the fire, Butler said.
It was not immediately known when the truck stop will reopen.