Venezuelan President Hugo Chavez has warned Colombia a strike against Farc rebels inside Venezuela like that in Ecuador on Saturday could start a war.
Reyes was Farc's first secretariat member to be killed in combat
He was speaking after Colombian air and ground forces killed a senior member of the leftist rebels operating just inside Ecuadorean territory.
Farc spokesman Raul Reyes died along with at least 16 other rebels and one Colombian soldier, Bogota said.
Ecuador has protested to Colombia over the incursion.
Venezuela's leftist leader has been mediating with Farc to secure the release of hostages the rebels hold.
The rebels recently freed four of about 40 political captives into the care of Mr Chavez.
Speaking at a televised meeting of his cabinet in Caracas on Saturday, Mr Chavez warned Colombia about attempting cross-border operations.
"Don't think about doing that over here because it would be very serious, it would be cause for war," he said.
The death of Reyes was described as the "biggest blow so far" to Farc by Colombian Defence Minister Juan Manuel Santos.
Reyes was killed in an air raid followed by a ground operation, the minister said.
The rebels had been in a camp 1.8km (1 mile) on the Ecuadorian side of the border across from the province of Putumayo when the attack was called in, Mr Santos said.
Colombian President Alvaro Uribe had earlier thanked Ecuador for its "co-operation", saying that "terrorism" did not respect borders.
Ecuadorean President Rafael Correa initially said he wanted clarification of the raid, which Mr Uribe had informed him about.
But Mr Correa has now said Ecuador will send a diplomatic note to protest at the "scandalous actions that are an aggression on our territory".
"The [Colombian] president either was poorly informed or brazenly lied to the president of Ecuador," Mr Correa said.
Reyes, 59, also known as Luis Edgar Devia, is the first member of Farc's ruling secretariat to be killed in combat in the group's 44-year history.
The BBC's Jeremy McDermott, in Medellin, says the military defeat of the Farc has been a cornerstone of President Uribe's administration since he came to power in 2002.
The killing of such a leading figure within Farc's secretariat means the group's aura of invincibility has evaporated, our correspondent adds.
With the ageing of Farc's leader, Manuel "Sureshot" Marulanda, Reyes had frequently been mentioned as a potential successor.
Colombia's government has received billions of dollars in aid to fight the guerrillas from the US administration which, along with the EU, views Farc as a terrorist organisation.
While Colombian troops have recently retaken control of areas previously held by rebel groups, Farc retains a strong hold over Colombia's more remote regions.